This project investigates the feasibility of treating non-resectable pulmonary cancers by perfusing the lungs in isolation with high concentrations of anticancer agents. A study was initially undertaken to investigate the kinetics of doxorubicin, an anticancer agent active against sarcoma, in situ perfused dog lungs. The procedure entailed inserting cannulae into the left pulmonary artery and left venous return, effectively isolating the left lobes from the systemic circulation. A wide range of perfusate doxorubicin concentrations was studied in order to determine the rate of drug uptake and retention in the lung tissue. Drug levels were determined using a specific high pressure liquid chromatographic assay. The kinetics of doxorubicin in the dog lungs were analyzed by modeling the data to a physiologicaly representative model of the perfusion technique. Doxorubicin was concentrated in dog lung during a 50 min perfusion. The uptake of drug increased with time but was saturable at perfusate concentrations exceeding 20 nmol/ml. Changes in the model parameters suggested that, at high perfusate concentrations, doxorubicin influx was inhibited. These studies have lead to a Phase I clinical trial utilizing the hemiperfusion technique in metastatic sarcoma patients. The surgical and perfusion procedures were successfully performed in all the patients examined to date. However, in human lung, doxorubicin accumulation was considerably slower than in the dogs. The concentration of drug in biopsied tumors from the patients was consistently less than the surrounding tissue.